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An update on NTM research - discovering cross-infection and beyond

Feature
- 16/10/2018

Approximately two years ago, important research funded by the Cystic Fibrosis Trust showed that a type of Non-Tuberculous Mycobacteria (NTM) can be transmitted between individuals with cystic fibrosis. As this week is International Infection Prevention Week, we’re giving you an update on how this research has progressed since then.

We’ve invested £1.5m into two Strategic Research Centres (SRCs), which are looking at understanding and developing treatments for NTM. The second centre began last year. Genetic studies of the bug led to new international guidelines about cross-infection, and also set us on a track to design new antibiotics. Find out more about this evolving research.

The story so far

Mycobacterium abscessus (M. abscessus)is the most common form of NTM causing lung infections in people with CF in the UK. Although it’s currently found in only a small proportion of patients (6% of people reported an NTM infection in 2017 according to the latest UK CF Registry report), it is a cause for concern because it is difficult to treat and can make people with CF ineligible for a lung transplant until they are clear of infection.

Macauley Tinston has had an NTM infection for four years, and said: “The day I was diagnosed with NTM, my fear of the condition only became even worse as I was aware there was limited research at the time. Daily treatment became a burden to me as two nebulisers a day became six. On top of that, I have a further three antibiotics to help suppress the impact of the condition.

“Although I tolerate the regime well, I can’t hide away from the fact that it’s exceptionally time-consuming - it’s something I’ve had to make time for. The antibiotics can make me feel nauseous, which is a massive pain and somewhat an intermittent disruption to my day, but I just have to get on with it.”

In 2016 a landmark research study was published showing that particular strains (or ‘clones’) of M. abscessushad recently evolved and spread around the world, becoming more virulent and causing more severe infections. The study provided evidence suggesting that transmission of M. abscessus could occur between individuals with CF, and that this probably happens through contaminated surfaces and aerosols. The study was funded by the Trust’s NTM Strategic Research Centre, led by Professor Andres Floto at the University of Cambridge.

Commenting at the time, Dr Janet Allen, Director of Strategic Innovation at the Trust, said: “This study exemplifies the enormous impact of Trust-funded Strategic Research Centres, which were designed to generate world-class research with the very highest impact. Without the support of the CF community, this landmark study would not have been possible.”

The research led to the development of international guidelines on cross-infection and managing NTM.

Getting to know NTM’s weaknesses

This research also identified the key genes that were responsible for virulence in M. abscessusthat could potentially be blocked by new therapies. Since then the researchers have been developing ways to study these new targets.

Honing in on the targets

Professor Floto and his international colleagues working on this SRC carried out several different approaches to investigate these targets in more detail. This involved:

Creating genetically modified versions of M. abscessus, inactivating each of the four gene targets in turn and testing any differences between the modified and unmodified bugs. Where these genes were inactivated, the toxicity of M. abscessus was reduced and so too was its ability to form a defensive layer (or ‘biofilm’).

Starting to design new drugs. The researchers working on this programme have pioneered a new way of developing new antibiotics called ‘fragment based design’ which uses the structure of proteins to build new drugs from small chemicals like lego blocks (known as fragments).

The painstaking work to understand more about the M. abscessus bug laid the foundations to develop new treatments. In 2017 the Trust awarded a second SRC grant to Professor Floto and his team, which carries the baton of developing new and more effective treatments for NTM.

Professor Floto said: “We’re delighted to have received funding to pursue this crucial challenge. We’re working with world-class experts and some fascinating new technologies, and hopefully we’ll come out the other side of this project with effective tools for fighting one of the most devastating infections that affects people with cystic fibrosis.”